{"doi":"10.1056/nejmoa1611925","title":"Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes","abstract":"Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).","journal":"New England Journal of Medicine","year":2017,"id":8674,"datarank":17.73090100728982,"base_score":8.922391597295857,"endowment":8.922391597295857,"self_citation_contribution":1.3383587395943786,"citation_network_contribution":16.39254226769544,"self_endowment_contribution":1.3383587395943786,"citer_contribution":16.39254226769544,"corpus_percentile":91.29373474369406,"corpus_rank":108,"citation_count":7714,"citer_count":193,"citers_with_citation_signal":193,"citers_with_endowment":193,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6233,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2017-08-17","fair_score":26.0417,"fair_percentile":7.739665787159191,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":75046,"name":"Vlado Perkovic","orcid":"0000-0002-4257-7620","position":1,"is_corresponding":false},{"id":75047,"name":"Kenneth W. Mahaffey","orcid":"0000-0002-3791-2148","position":2,"is_corresponding":false},{"id":29444,"name":"Dick de Zeeuw","orcid":"0000-0003-3434-7777","position":3,"is_corresponding":false},{"id":75048,"name":"Greg Fulcher","orcid":null,"position":4,"is_corresponding":false},{"id":62622,"name":"Ngozi Erondu","orcid":null,"position":5,"is_corresponding":false},{"id":75049,"name":"Wayne Shaw","orcid":null,"position":6,"is_corresponding":false},{"id":75050,"name":"Gordon Law","orcid":null,"position":7,"is_corresponding":false},{"id":75051,"name":"Mehul Desai","orcid":"0000-0003-3489-1967","position":8,"is_corresponding":false},{"id":74614,"name":"David R. Matthews","orcid":"0000-0001-6504-0036","position":9,"is_corresponding":false},{"id":923,"name":"Bruce Neal","orcid":"0000-0002-0490-7465","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":32.5,"fair_a":42.5,"fair_i":12.5,"fair_r":16.6667,"fair_zscore":-1.734,"fair_rationale":{"fair_score":26.04,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":32.5,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"datacite=0, pmcid=False, pmid=False","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper provides only human-readable metadata (abstract, title, authors, journal metadata) without any evidence of machine-readable semantic markup or structured data formats."}]},"A":{"name":"Accessible","score":42.5,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"While clinical trial registration numbers are provided, there is no clear protocol for accessing the underlying data or code; 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